MRD-Guided Aumolertinib-Based Adjuvant Therapy for Resected EGFR-Mutant NSCLC

Registry record from ClinicalTrials.gov (NCT07873086). This is a study registration, not published results. Lead sponsor: Peking University People's Hospital. Recruitment status: NOT_YET_RECRUITING. Phase: NA. Study type: INTERVENTIONAL. Enrollment: 50 participants (ESTIMATED). Conditions: Non-Small Cell Lung Cancer. Interventions: DRUG: Aumolertinib; DRUG: Pemetrexed; DRUG: Carboplatin. Primary outcome measures: 2-year disease-free survival (DFS) rate , 24 months after surgery. Brief summary: Despite complete (R0) resection, patients with EGFR-mutant stage IIA-IIIB non-small cell lung cancer (NSCLC) still face a substantial risk of postoperative recurrence. Although adjuvant EGFR tyrosine kinase inhibitors have improved disease-free survival, conventional fixed-duration adjuvant therapy is applied uniformly to all patients and does not distinguish those who genuinely require treatment from those who could be safely spared. Circulating tumor DNA (ctDNA) profiling enables minimal residual disease (MRD) detection that is both earlier and more accurate than imaging, and has therefore emerged as a promising tool for individualizing postoperative adjuvant therapy. This prospective, real-world, interventional study will enroll 50 patients with resected (R0), EGFR 19del or L858R mutant, stage IIA-IIIB non-squamous NSCLC. For three years after surgery, adjuvant treatment is dynamically guided by serial MRD testing performed 3-10 days and 4 weeks (±7 days) after surgery and every 3-6 months thereafter. Patients with a positive MRD result at either of the first two time points receive aumolertinib-based adjuvant therapy, with the regimen determined by the mutations detected in blood: aumolertinib monotherapy (110 mg once daily) when only the EGFR mutation is detected, or aumolertinib combined with chemotherapy (pemetrexed plus carboplatin for four cycles, followed by pemetrexed maintenance) when co-mutations are detected. Patients whose MRD remains negative undergo observation with regular ctDNA monitoring; if MRD turns positive or imaging progression occurs, aumolertinib-based adjuvant therapy is initiated according to the same rules. Treatment is discontinued once MRD becomes undetectable; patients with persistently negative MRD over three years receive no aumolertinib. After three years, subsequent treatment is at the investigator's discretion. The primary endpoint is the 2-year disease-free survival (DFS) rate, defined as the proportion of patients remaining free from recurrence or death for at least 24 months after surgery. Secondary endpoints include the 2-, 3-, and 5-year overall survival rates, 3-year total treatment cost, incremental cost-effectiveness ratio, rate of timely postoperative recurrence diagnosis, and cumulative duration of aumolertinib treatment; exploratory analyses will assess the association between ctDNA/MRD molecular features and clinical efficacy. This study aims to establish a dynamic MRD-guided precision adjuvant strategy that avoids overtreatment while improving outcomes in resected EGFR-mutant NSCLC.